Phenotypic Changes in Resident Corneal Dendritic Cells in Response to Inflammation

Abstract

Abstract: : Purpose: Dendritic cells (DC) comprise a system of highly efficient antigen-presenting cells which initiate immune responses. We have recently shown that a heterogeneous population of bone marrow (BM)-derived DC reside in the normal corneal stroma. The purpose of this study was to examine the phenotype and distribution of these cells in corneal inflammation Methods: Normal, inflamed and transplanted corneas of several murine strains were excised at different timepoints and immunofluorescence single- and double-staining for CD11c, CD11b, CD45, CD80 (B7.1), CD86 (B7.2), CD3, and MHC class II (Ia) was performed by confocal microscopy on wholemount corneal stromas to characterize and evaluate the distribution of DC in inflammation. Results: CD11c⁺CD11b⁺ BM-derived DC, present in the anterior stroma, were nearly one-half MHC class II⁺CD80⁺CD86⁺in the periphery, while they were uniformly MHC class II^—CD80^—CD86^— in the center in the normal cornea. In the inflamed cornea, there was a significant increase in the number of DC. More importantly, a majority of DC had upregulated their expression of MHC class II, CD80, and CD86, indicating their state of maturation. The upregulation of these maturation markers was confirmed by transplantation experiments, where MHC class II^— DC in donor buttons expressed MHC class II as early as 24 hours after transplantation at the graft-host border. In addition, a CD11c^— CD11b⁺ population of monocytes/ macrophages, present almost exclusively in the posterior stroma of the normal cornea, was seen throughout all stromal layers in increased numbers during inflammation. Conclusions: We describe for the first time that immature/precursor resident stromal DC of the cornea are capable of expressing MHC class II antigen and maturation after inflammation and surgery. Our results suggest that the cornea is capable of participating in immune and inflammatory responses by virtue of its own heterogeneous population of DC.

Keywords: cornea: stroma and keratocytes • inflammation • cornea: basic science